Bio 655 Week 1 Lab Report

Dr. Colleen Winters – BIO 655
Vishall G. Kaistha

TITLE:
“Recombination-Directed DNA Repair Promote Homologous Stimulating Transcription of Genes That That Preserves Genomic Integrity by MEN1 Is a Melanoma Tumor Suppressor”. Minggang Fang, Fen Xia, Meera Mahalingam, Ching-Man Virbasius, Narendra Wajapeyee and Michael R. Green. (May, 2013)

INTRODUCTION:
MEN1 is a protein localized in the nucleus that is known to assist in various cellular activates involving cell cycle regulation, transcription, and cellular proliferation. Mutations in the MEN1 gene that result in its loss of function are linked to multiple endocrine neoplasia type 1. This type of familial cancer syndrome is an inherited autosomal dominant disease which results in an increased

The study also found that an increase in γ-H2AX (a marker for DNA double-strand breaks) and a decrease in RAD1 (a marker of HR directed DNA repair) focus-positive cells was associated with a depletion of MEN1 expression as predicted. The study also predicted that NHEJ could function to repair double strand breaks, and would increase with a loss of MEN1 functionality. The study found this prediction to be true. The study also investigated the role of ATM and ATR DNA damage kinases in relation to MEN1, and found that MEN1 is protected from ubiquitin mediated degradation through phosphorylation by ATM and ATR protein kinases. One of the most significant results from this study involved determining the functional relationship between the expression of HR target genes and MEN1, as well as investigating the mechanism of action involved in the cellular process. The study found that MEN1 stimulates transcription of several genes, and more specifically that BRCA1, RAD51, and RAD51AP1 are direct targets of MEN1, and that MEN1 and BRCA1 possess a strong correlation between one another (1). The model mechanism of MEN1’s overall functionality is probably the most significant result of this study. The study revealed that MEN1 promotes genome integrity by directly

It was interesting and informative on a specific topic I previously knew little about, and all the methods, results, and conclusions were clearly conveyed and easily comprehended. What I liked most about this study was how each individual experimental result was used to piece together the mechanism in which MEN1 was operating under to promote HR directed DNA repair and preserve genomic integrity. Although the experimental design utilized in this study seemed quite complex and thorough, I thought the process was quite interesting and unique, as well as completely relevant and necessary for the study to achieve the results and conclusions they had found. I also really liked the way the paper was organized. It was written in a way that made me feel as if I was learning the results in the same way they were discovered by those carrying out the study. More importantly, the paper did an excellent job of explaining the significance of every result, allowing the reader to understand the relevance and implications attached with every finding. For example, when the paper found that MEN1 is phosphorylated by ATM and ATR kinases to avoid ubiquitin-mediated degradation, its explanation went beyond what many papers would include in regards to the relevance of the phosphorylation activity. It not only broke down and explained the process of how MEN1 phosphorylation protected it